A variety of human ailments owe their origin to pathogenic microorganisms, which include bacteria, virus and fungi. The presence of such pathogenic microorganisms lead to septicaemia, serious infections of upper and lower respiratory tract, CNS, meningitis, intra-abdominal including peritoneum, genito-urinary tract, skin, and soft tissue, and variety of other infections like systemic mycosis, candidiasis including infections caused by dermatophytes. During last 100 years, significant progress has been made to combat the diseases caused by such a large family of microbes with innumerable therapeutic agents of diverse chemical and biological nature that have become available as a short and long term cure. Such antimicrobials include aminoglycosides, penicillins, cephalosporins, macrolides, glycopeptides, fluoroquinolones, tetracyclins, first and second line anti-TB drugs, anti-leprosy, anti-virals, polyene, triazole and imidazole anti-fungals, combinations like pyrimidine derivatives and trimethoprim and sulphamethoxizole.
While such agents are effective against pathogenic bacteria and fungi and therefore useful in the treatment of disease conditions associated with the presence of such pathogens, there is increasing evidence that use of such agents has certain limitations and led to clinical concern. There are several such factors responsible for such a concern: (a) certain strains of bacteria and fungi become increasingly resistant to one or more of the known anti-infectives and therefore the usual or standard therapeutic doses lead to less beneficial effect, (b) higher doses that are required to combat the disease cause undesirable side effects and toxicity, and (c) high-cost of treatment and patient-non-compliance. The emergence of drug-resistant pathogenic organisms has also been attributed to uncontrolled antibiotic overuse and under use and even under dosing, irrational frequency of administration. The prolonged and high dose therapy is also a matter of serious concern particularly in pregnant women, geriatrics and children.
While an approach embodying rational use of antibiotics may help slow the problem of microbial drug resistance, new antimicrobial agents must be discovered to combat those strains that are now resistant to most, if not all, currently available antibiotics. As such, there is a continued interest in the identification of novel antimicrobial agents, which can be used to further supplement the medical practitioner's armamentarium against pathogenic microorganisms
In another approach, two anti-infectives are combined in such a way that the combination produces synergy i.e. one of the anti-infectives acts as the potentiator of the other anti-infective. The example of such combination is Trimethoprim-Sulfamethoxazole also known as co-trimoxazole or TMP-SMX, which was introduced in 1968 as a broad-spectrum antimicrobial agent. Trimethoprim was specially developed as a potentiator of sulphonamide to act synergistically against bacteria and delay the development of bacterial resistance.
The 1:5 ratio of trimethoprim:sulfamethoxazole achieves an approximate 1:20 ratio of peak serum concentrations which is the optimal synergistic ratio of serum concentrations against most susceptible bacteria (Gutman L T, Pediatr Infect Dis 1984;3:349-57, Olin B R, Facts and Comparisons, Inc. 1998; 408b-409d, Cockerill F R, Edson R S, Mayo Clin Proc 1991; 66:1260-9).
The combination can also be between one anti-infective agent and another chemical agent which by itself is not anti-infective in nature but when in combination, enhances the effectiveness of the anti-infective drug. The example of such combination is Amoxicillin+Clavulanic acid, more commonly known as Augmentin. Amoxicillin is an antibiotic of the penicillin type. It is effective against different bacteria such as H. influenzae, N. gonorrhea, E. coli, Pneumococci, Streptococci, and certain strains of Staphylococci. Chemically, it is closely related to penicillin and http://www.asiamedicinenet.com/script/main/art.asp?li=AMN&ArticleKey=693 ampicillin. Addition of Clavulanic acid to Amoxicillin in Augmentin enhances the effectiveness of this antibiotic against many other bacteria that are ordinarily resistant to amoxicillin. Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally related to the penicillins and possesses the ability to javascript:defwindow(‘inactivate’) inactivate a wide variety of β-lactamases by javascript:defwindow(‘blocking’) blocking the active sites of these enzymes. Clavulanic javascript:defwindow(‘acid’)acid is particularly active against the clinically important javascript:defwindow(‘plasmid’) plasmid mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins.